N-TERMINAL PEPTIDES OF SDF-1 HAVE FUNCTIONAL ACTIVITIES MEDIATED BY CXCR4

摘要

Peptides correspond ing to the N-terminal 9 residues of stromal cell derivedfactor-1 (SDF-1) have SDF-1activity. Peptides, corresponding to residues 1-8, 1-9, and a disulfide linkeddimer of 1-9, involvingCys-9, induced chemotaxis in T lymphocytes and CEM cells, and bound the SDF-1receptor, CXCchemokine receptor 4 (CXCR4). The peptides had similar activities to SDF-1,but were less potent.Whereas native SDF-I had half maximal chemoattractant activity at 5 nM, the 1-9 direr and a 1-9monomer analog were 100- and 3600-fold less potent, respectively. Receptordesensitization andcompetition binding experiments indicated that the SDF-1 peptides are specificfor CXCR4. As Cys-9 isinvolved in a disulfide bridge with Cys 34 in native SDF-1, it is possiblethat the disulfide of the peptidedimer enhances its structural similarity to the native protein. Overall thisstudy shows that the N-terminalregion is sufficient to bind and activate CXCR4, which suggests thefeasibility of designing smallCXCR4 agonists or antagonists.